The Clinical Character Of Hand Foot And Mouth Disease And Molecular Character Of Human Enterovirus71in Changchun

Hand, foot and mouth disease is a global infectious disease which causedby multiple enterovirus and commonly affect children who younger than5years old. Most patients had mild symptoms and resolves spontaneously within10–14days, but a small proportion of them may suffer from severecomplications such as aseptic meningitis, encephalitis, acute flaccid paralysis,pulmonary edema,myocarditis and even death. The prevalence of HFMD inthe Asia-Pacific region has increased greatly since1997and there were severalepidemics in mainland China in the past few years. It is a serious threat tohealth of people, especially children in our country. As HFMD is lifethreatening for children, the disease was listed as one of the category "C"notifiable diseases in China since2nd May2008. The epidemic may furtherexpand, and how to prevent the disease is still very important in future. Atpresent there is no specific treatment, specific vaccines and antiviral drugs.Therefore, the clinical characteristics of HFMD and the research of biology,pathogenesis, diagnosis and prevention of enterovirus71are extremelynecessary.There are20types of human enterovirus can cause hand foot mouthdisease, including enterovirus71, coxsackievirus A16,4,5,9,10and coxsac-kievirus B2,5,as well as echovirus etc.. Among of them EV71and CA16arethe most common pathogene.Coxsackievirus A16was main pathogene before1970s, however, EV71hadbecome the leading pathogene of hand, foot and mouth disease since1990s.Human enterovirus71(EV71)-associated hand, foot, and mouth disease (HFMD) has been a leading cause of childhood infection in China since2008.Epidemic and molecular characteristics of HFMD have been examined in manyareas of China, including the central and southern regions. However, clinicaland genetic characterization of EV71in the northeastern region of China isscarce. We studied the clinical characteristics of hand foot and mouth diseasefrom the first hospital of Jilin University. Part of HFMD patients werediagnosed enterovirus types by real-time PCR. Seven EV71strains wereisolated from from severe and mild disease patients and sequenced, then weresubjected to phylogenetic and recombination analysis.The seasonal peak occurred from June to September in Changchun. Moremales were affected than females and more than93%HFMD patients were lessthan5years old. The age peak appeared in the groups of1–2years old, andwith age growing the numbers of HFMD cases reduced. The number of patientsbegan to rise from three months old less than one year old patients.The numberof HFMD patients in rural areas were significantly higher than those in urbanareas. A total of17HFMD death cases from2008to2010were collected. Meanage at onset was1.41years old (range6month to3years)；The mean length ofhospital stay was only1.4days, most patients die within24hours of admission.All cases complicated with fevers and neurologic complications, There were9patients been detecten by PCR and all of them were identified EV71infection.HFMD outbreak is mainly caused by EV71in Changchun, Thecomplications were more frequent and serious in patients with EV71infectionthan those with CA16and other enterovirus. The complications were mild inpatients with with CA16. But other enterovirus also resulted in neurologiccomplications, pulmonary complication, which reached about28%in all theenterovirus. Molecular analysis showed that these enterovirus were neitherEV71nor CA16. In this study, a series of analyses were performed on seven full-lengthEV71sequences from HFMD patients who had either severe or mild disease.We have determined that these seven circulating EV71viruses from Changchun,China are actually complex recombinant viruses involving multiple type Ahuman enterovirus (HEV). Classified as EV71subtype C4(EV71C4), theseChangchun EV71viruses contain genetic recombination events between theCA4, CA5, EV71B4and EV71C1strains. Most of the structural protein region(P1) of these viruses resembled that of the prototype EV71C1strains. Thenon-structural protein domains (P2and P3) showed a high degree of similaritywith CA4, CA5and EV71B4in different regions. The5'UTR hadunclassified recombination,while partial3D region of these viruses showed ahigh degree of similarity to CA16. Phylogenetic analysis of full-length orpartial sequences of isolates from severe or mild disease patients in Changchunalways formed a single cluster in various phylogenetic analysis of differentgenomic regions, suggesting that all seven strains originated from one singlecommon ancestor. There was no correlation between viral genomic sequenceand virulence. Thus, we found that circulating recombinant forms of EV71are prevalent among HFMD patients in Northeastern China. The existence of aunique cluster of EV71related viruses in Northeast China has importantimplications for vaccine development that would address the increasingprevalence of HFMD.